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1.
Int J Biol Macromol ; 278(Pt 2): 134491, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39111495

RESUMEN

The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-ß. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment.

2.
Chem Asian J ; : e202400741, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39058306

RESUMEN

Achieving the concurrent manifestation of thermally activated delayed fluorescence (TADF) and aggregation-induced emission (AIE) within a single molecular system is highly sought after for organic light-emitting diodes (OLEDs), yet remains rare. In this study, we present a novel TADF-AIE dye, named PQMO-PXZ, which has been designed, synthesized, and systematically characterized. Our comprehensive investigation, which includes structural analysis, theoretical calculations, and optical studies, evaluates the potential of PQMO-PXZ for integration into OLEDs. Unlike existing azaryl-ketone-based emitters, PQMO-PXZ exhibits red-shifted emission and enhanced luminescence efficiency, due to its rigid structure and strong intramolecular charge transfer characteristics. Significantly, PQMO-PXZ demonstrates pronounced AIE properties and TADF with a short delayed lifetime. When utilized as the emissive core, OLED devices based on PQMO-PXZ achieve a respectable external quantum efficiency of up to 11.8% with minimal efficiency roll-off, underscoring PQMO-PXZ's promise as a highly efficient candidate for OLED applications.

3.
Chem Commun (Camb) ; 60(61): 7946-7949, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38984894

RESUMEN

A through-space charge transfer pyrene-based fluorophore has been developed for organic light-emitting devices (OLEDs). This material exhibits deep-blue fluorescence, bipolar characteristics, and anti-quenching behavior in the solid state. It proves to be an effective emitter for both doped and nondoped deep-blue OLEDs.

4.
Pest Manag Sci ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39017029

RESUMEN

BACKGROUND: Controlling the spread of arboviral diseases remains a considerable challenge due to the rapid development of insecticide resistance in Aedes mosquitoes. This study evaluated the effects of boric acid-containing toxic sugar bait (TSB) on field populations of resistant Aedes aegypti mosquitoes. In addition, this study examined the flight activity and wing beat frequency and amplitude of males and the flight activity, fecundity, and insemination of females after pairing with males exposed to TSB. The population dynamics of Aedes mosquitoes under imbalanced sex ratios were examined to simulate realistic field conditions for male suppression under the effect of TSB. RESULTS: The mortality of male mosquitoes was consistently high within 24 h after exposure. By contrast, the mortality of female mosquitoes was inconsistent, with over 70% mortality observed at 168 h. The flight activity and wing beat amplitude of treated males were significantly lower than those of controls, but no significant difference in wing beat frequency was detected. The fecundity and insemination of treated female mosquitoes were lower than those of controls. A simulation study indicated that considerably low male population densities led to mating failures, triggering a mate-finding Allee effect and resulting in persistently low population levels. CONCLUSION: Boric acid-containing TSB could effectively complement current chemical intervention approaches to control resistant mosquito populations. TSB is effective in reducing field male populations and impairing male flight activity and female-seeking behavior, resulting in decreased fecundity and insemination. Male suppression due to TSB potentially results in a small mosquito population. © 2024 Society of Chemical Industry.

5.
World J Gastrointest Surg ; 16(6): 1803-1824, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38983344

RESUMEN

BACKGROUND: Stomach adenocarcinoma (STAD) is one of the main reasons for cancer-related deaths worldwide. This investigation aimed to define the connection between STAD and Cuproptosis-related genes (CRGs). Cuproptosis is a newly identified form of mitochondrial cell death triggered by copper. AIM: To explore the identification of potential biomarkers for STAD disease based on cuproptosis. METHODS: A predictive model using Gene Ontology (GO), Least Absolute Shrinkage and Selection Operator (LASSO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis analyzed gene interconnections, focusing on 3 copper-related genes and their expression in The Cancer Genome Atlas-STAD. Networks for mRNA-miRNA and mRNA-transcription factor interactions were constructed. The prognostic significance of CRG scores was evaluated using time-receiver operating characteristic, Kaplan-Meier curves, and COX regression analysis. Validation was conducted with datasets GSE26942, GSE54129, and GSE66229. Expression of copper-related differentially expressed genes was also analyzed in various human tissues and gastric cancer subpopulations using the human protein atlas. RESULTS: Three significant genes (FDX1, LIAS, MTF1) were identified and selected via LASSO analysis to predict and classify individuals with STAD into high and low CRG score subgroups. These genes were down-regulated in both risk categories. GO and KEGG analyses highlighted their involvement mainly in the electron transport chain. After validating their differential expression, FDX1 emerged as the most accurate diagnostic marker for gastric cancer. Additionally, the RCircos package localized FDX1 on chromosome 11. CONCLUSION: Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy, providing new ideas for further scientific research.

6.
MycoKeys ; 106: 303-325, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38993357

RESUMEN

Species of the family Microdochiaceae (Xylariales, Sordariomycetes) have been reported from worldwide, and collected from different plant hosts. The proposed new genus and two new species, viz., Macroidriella gen. nov., M.bambusae sp. nov. and Microdochiumaustrale sp. nov., are based on multi-locus phylogenies from a combined dataset of ITS rDNA, LSU, RPB2 and TUB2 with morphological characteristics. Microdochiumsinense has been collected from diseased leaves of Phragmitesaustralis and this is the first report of the fungus on this host plant. Simultaneously, we annotated 10,372 to 11,863 genes, identified 4,909 single-copy orthologous genes, and conducted phylogenomic analysis based on genomic data. A gene family analysis was performed and it will expand the understanding of the evolutionary history and biodiversity of the Microdochiaceae. The detailed descriptions and illustrations of species are provided.

7.
J Int Med Res ; 52(6): 3000605241259682, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38886869

RESUMEN

OBJECTIVE: To compare the staining quality between rapid hematoxylin and eosin (H&E) staining and routine H&E staining of frozen breast tissue sections. METHODS: In this cross-sectional observational study, 120 frozen breast tissue sections were randomly assigned to rapid or routine H&E staining (n = 60 per group). Rapid H&E staining used a 7:1 mixture of modified Gill's hematoxylin and alcohol-soluble 1% eosin Y. The staining quality of each section was evaluated and scored. A score of >7 was considered excellent, a score of 6 to 7 good, and a score of ≤5 poor. RESULTS: The staining time for rapid staining was approximately 3 minutes, whereas that of routine staining was approximately 12 minutes. There were no significant differences in the staining quality scores or proportions of sections in each grade between the two staining methods. The proportions of sections that were classified as excellent or good were 96.7% and 98.3% for rapid and routine staining, respectively. CONCLUSIONS: In frozen breast tissue sections, rapid H&E staining may provide staining quality that is comparable to that of routine staining, while markedly reducing the staining time.


Asunto(s)
Mama , Eosina Amarillenta-(YS) , Secciones por Congelación , Hematoxilina , Coloración y Etiquetado , Humanos , Femenino , Coloración y Etiquetado/métodos , Secciones por Congelación/métodos , Mama/patología , Estudios Transversales , Persona de Mediana Edad , Adulto , Neoplasias de la Mama/patología , Anciano
8.
Front Pharmacol ; 15: 1284371, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38881872

RESUMEN

Background: Cynanchum paniculatum (Bunge) Kitag. ex H.Hara, a member of the Asclepiadaceae family, has a rich history as a traditional Chinese medicinal plant used to treat digestive disorders. However, its potential anti-cancer effects in pancreatic cancer remain largely unexplored. Aim: This study delves into the intricate anti-pancreatic cancer mechanisms of C. paniculatum (Bunge) Kitag. ex H.Hara aqueous extract (CPAE) by elucidating its role in apoptosis induction and the inhibition of invasion and migration. Methods: A comprehensive set of methodologies was employed to assess CPAE's impact, including cell viability analyses using MTT and colony formation assays, flow cytometry for cell cycle distribution and apoptosis assessment, scratch-wound and Matrigel invasion assays for migration and invasion capabilities, and immunoblotting to measure the expression levels of key proteins involved in apoptosis and metastasis. Additionally, a murine xenograft model was established to investigate CPAE's in vivo anti-cancer potential. Results: CPAE exhibited time- and dose-dependent suppression of proliferation and colony formation in pancreatic cancer cells. Notably, CPAE induced apoptosis and G2/M phase arrest, effectively activating the caspase-dependent PARP pathway. At non-cytotoxic doses, CPAE significantly curtailed the metastatic abilities of pancreatic cells, effectively suppressing epithelial-mesenchymal transition (EMT) and downregulating the TGF-ß1/Smad2/3 pathway. In vivo experiments underscored CPAE's ability to inhibit tumor proliferation. Conclusion: This study illuminates the multifaceted anti-proliferative, pro-apoptotic, anti-invasive, and anti-migratory effects of CPAE, both in vitro and in vivo. CPAE emerges as a promising herbal medicine for pancreatic cancer treatment, with its potential mediated through apoptosis induction via the caspase-dependent PARP pathway and MET suppression via the TGF-ß1/Smad2/3 signaling pathway at non-cytotoxic doses. These findings advocate for further exploration of CPAE's therapeutic potential in pancreatic cancer.

9.
World J Clin Cases ; 12(17): 3130-3137, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38898845

RESUMEN

BACKGROUND: Neurological complications are common in the management of venoarterial extracorporeal membrane oxygenation (VA-ECMO), with most patients requiring sedation and intubation, limiting the assessment of neurological function. There-fore, we must rely on advanced neuroimaging techniques, such as computed tomography angiography (CTA) and computed tomography perfusion (CTP). Because ECMO changes the normal blood flow pattern, it may interfere with the contrast medium in some special cases, leading to artifacts and ultimately mis-leading clinical decisions. CASE SUMMARY: A 61-year-old man presented to a local hospital with chest tightness and pain 1 d prior to presentation. The patient was treated with VA-ECMO after sudden car-diac and respiratory arrest at a local hospital. For further treatment, the patient was transferred to our hospital. The initial consciousness assessment was not clear, and routine CTP was performed to understand the intracranial changes, which suggested a large area of cerebral infarction on the right side; however, the cerebral oxygen was not consistent with the CTP results, and the reexamination of CTA still suggested a right cerebral infarction. To identify this difference, bedside transcranial Doppler was performed, and the blood flow on both sides was different. By reducing the ECMO flow, CTP reexamination showed that the results were normal and consistent with the clinical results. On day 3, the patient was alert and showed good limb movements. CONCLUSION: In patients with peripheral VA-ECMO, cerebral perfusion confirmed by CTP and CTA may lead to false cerebral infarction.

10.
World J Stem Cells ; 16(5): 575-590, 2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38817328

RESUMEN

BACKGROUND: Atherosclerosis (AS), a chronic inflammatory disease of blood vessels, is a major contributor to cardiovascular disease. Dental pulp stem cells (DPSCs) are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflammation-related diseases. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases. AIM: To modify DPSCs with HGF (DPSC-HGF) and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout (ApoE-/-) mouse model and an in vitro cellular model. METHODS: ApoE-/- mice were fed with a high-fat diet (HFD) for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs (DPSC-Null) through tail vein at weeks 4, 7, and 11, respectively, and the therapeutic efficacy and mechanisms were analyzed by histopathology, flow cytometry, lipid and glucose measurements, real-time reverse transcription polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay at the different time points of the experiment. An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells (HAOECs), and indirect co-cultured with supernatant of DPSC-Null (DPSC-Null-CM) or DPSC-HGF-CM, and the effect and mechanisms were analyzed by flow cytometry, RT-PCR and western blot. Nuclear factor-κB (NF-κB) activators and inhibitors were also used to validate the related signaling pathways. RESULTS: DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors, and the percentage of macrophages in the aorta, and DPSC-HGF treatment had more pronounced effects. DPSCs treatment had no effect on serum lipoprotein levels. The FACS results showed that DPSCs treatment reduced the percentages of monocytes, neutrophils, and M1 macrophages in the peripheral blood and spleen. DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-α stimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway. CONCLUSION: This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/- mice on a HFD, and could be of greater value in stem cell-based treatments for AS.

11.
Am J Sports Med ; 52(7): 1707-1718, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38702986

RESUMEN

BACKGROUND: The tendon-bone interface (TBI) in the rotator cuff has a poor intrinsic capacity for healing, which increases the risk of retear after rotator cuff repair (RCR). However, facilitating regeneration of the TBI still remains a great clinical challenge. Herein, the authors established a novel strategy based on magnetic seeding to enhance the TBI regeneration. HYPOTHESIS: Magnetic seeding bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide (SPIO-BMSCs) into a biphasic scaffold can promote tendon-bone healing after RCR. STUDY DESIGN: Controlled laboratory study. METHODS: BMSCs were labeled with SPIOs. Prussian blue staining, CCK-8 tests, Western blot, and quantitative reverse transcription polymerase chain reaction (PCR) were used to determine the optimal effect concentration of SPIOs on cell bioactivities and abilities. Then SPIO-BMSCs were magnetically seeded into a biphasic scaffold under a magnetic field. The seeding efficacy was assessed by a scanning electron microscope, and the potential mechanism in chondrogenic differentiation after seeding SPIO-BMSCs into the scaffold was evaluated by Western blot and PCR. Furthermore, the effect of SPIO-BMSC/biphasic scaffold on tendon-bone healing after RCR using a rat model was examined using histological analysis, enzyme-linked immunosorbent assay, and biomechanical evaluation. RESULTS: BMSCs labeled with 100 µg/mL SPIO had no effect on cell bioactivities and the ability of chondrogenic differentiation. SPIO-BMSCs were magnetically seeded into a biphasic scaffold, which offered a high seeding efficacy to enhance chondrogenic differentiation of SPIO-BMSCs via the CDR1as/miR-7/FGF2 pathway for TBI formation in vitro. Furthermore, in vivo application of the biphasic scaffold with magnetically seeded SPIO-BMSCs showed their regenerative potential, indicating that they could significantly accelerate and promote TBI healing with superior biomechanical properties after RCR in a rat rotator cuff tear model. CONCLUSION: Magnetically seeding SPIO-BMSCs into a biphasic scaffold enhanced seeding efficacy to promote cell distribution and condensation. This construct enhanced the chondrogenesis process via the CDR1as/miR-7/FGF2 pathway and further promoted tendon-bone healing after RCR in a rat rotator cuff tear model. CLINICAL RELEVANCE: This study provides an alternative strategy for improving TBI healing after RCR.


Asunto(s)
Células Madre Mesenquimatosas , Ratas Sprague-Dawley , Lesiones del Manguito de los Rotadores , Andamios del Tejido , Cicatrización de Heridas , Animales , Lesiones del Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/terapia , Células Madre Mesenquimatosas/fisiología , Ratas , Masculino , Manguito de los Rotadores/cirugía , Trasplante de Células Madre Mesenquimatosas , Nanopartículas Magnéticas de Óxido de Hierro , Diferenciación Celular , Condrogénesis
12.
Alpha Psychiatry ; 25(2): 183-189, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38798803

RESUMEN

Objective: To explore the association between malnutrition and risk of depression in the elderly. Methods: Relevant studies were searched in PubMed, Web of Science, the Cochrane Library, Scopus, and Embase from the establishment of the database to August 17, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata16.0 software was used for meta-analysis. Results: A total of 8 observational studies were identified with 11 112 participants, of which 2771 elderly patients had depression. The meta-pooled results showed a significant correlation between nutritional status and depression risk (odds ratio (OR) = 2.03, 95% CI = (1.47, 2.81), P < 0.001). Subgroup analysis found that the malnutrition scores of different study types and the diagnostic methods of depression and malnutrition were correlated with the risk of depression. Conclusion: Malnutrition was associated with depression risk in the elderly. Further large-scale multicenter studies should be conducted to test and verify the results.

13.
Kaohsiung J Med Sci ; 40(6): 530-541, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38647095

RESUMEN

We previously found that the relative abundance of Bifidobacterium was increased after chemotherapy; however, the role of Bifidobacterium longum in chemotherapeutic drug resistance in ovarian cancer (OVC) remains unclear. This study aimed to understand the potential effects and mechanism of B. longum extracellular vesicles (B. longum-EVs) on carboplatin (CBP) resistance in OVC. Eight normal and 11 ovarian tissues were collected and the expression of B. longum genomic DNA and its association with acquired CBP resistance in OVC patients was determined. After isolating EVs by ultracentrifugation from B. longum (ATCC 15707), CBP-resistant A2780 cells were treated with PBS, CBP, B. longum-EVs, or CBP + B. longum-EVs, and subsequently analyzed by CCK-8, Edu staining, Annexin V/PI double staining, wound healing, and Transwell assays to detect cell viability, proliferation, apoptosis, migration, and invasion, respectively. MRP1, ATP7A, ATP7B, and p53 expression as well as p53 phosphorylation were measured by western blot analysis. S15A mutation of p53 was assessed to examine the potential role of p53 Ser15 phosphorylation in CBP-resistant OVC. B. longum levels were elevated and positively associated with CBP resistance in OVC patients. Only high concentrations of B. longum-EVs attenuated A2780 cell proliferation, apoptosis, migration, and invasion. B. longum-EVs exposure significantly enhanced the sensitivity of CBP-resistant A2780 cells to CBP and decreased the expression of drug resistance-related proteins. The effect of B. longum-EVs on reversing CBP resistance was completely inhibited by S15A mutation of p53. B. longum-EVs enhanced the sensitivity of OVC cells to CBP through p53 phosphorylation on Ser15.


Asunto(s)
Bifidobacterium longum , Carboplatino , Resistencia a Antineoplásicos , Vesículas Extracelulares , Neoplasias Ováricas , Proteína p53 Supresora de Tumor , Humanos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Femenino , Fosforilación , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/tratamiento farmacológico , Vesículas Extracelulares/metabolismo , Carboplatino/farmacología , Carboplatino/uso terapéutico , Línea Celular Tumoral , Bifidobacterium longum/metabolismo , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos
14.
J Med Chem ; 67(8): 6313-6326, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38574345

RESUMEN

Coactivator-associated arginine methyltransferase 1 (CARM1), an important member of type I protein arginine methyltransferases (PRMTs), has emerged as a promising therapeutic target for various cancer types. In our previous study, we have identified a series of type I PRMT inhibitors, among which ZL-28-6 (6) exhibited increased activity against CARM1 while displaying decreased potency against other type I PRMTs. In this work, we conducted chemical modifications on compound 6, resulting in a series of (2-(benzyloxy)phenyl)methanamine derivatives as potent inhibitors of CARM1. Among them, compound 17e displayed remarkable potency and selectivity for CARM1 (IC50 = 2 ± 1 nM), along with notable antiproliferative effects against melanoma cell lines. Cellular thermal shift assay and western blot experiments confirmed that compound 6 effectively targets CARM1 within cells. Furthermore, compound 17e displayed good antitumor efficacy in a melanoma xenograft model, indicating that this compound warrants further investigation as a potential anticancer agent.


Asunto(s)
Antineoplásicos , Melanoma , Proteína-Arginina N-Metiltransferasas , Humanos , Proteína-Arginina N-Metiltransferasas/antagonistas & inhibidores , Proteína-Arginina N-Metiltransferasas/metabolismo , Animales , Melanoma/tratamiento farmacológico , Melanoma/patología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Ratones , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos , Ensayos de Selección de Medicamentos Antitumorales
15.
Cell Commun Signal ; 22(1): 164, 2024 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448900

RESUMEN

Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.


Asunto(s)
Neoplasias Hepáticas , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Secuenciación del Exoma , Tumores Neuroendocrinos/genética , Genómica , Neoplasias Hepáticas/genética , Neoplasias Pancreáticas/genética , Microambiente Tumoral
17.
Eur J Med Chem ; 269: 116288, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38460270

RESUMEN

Coactivator-associated arginine methyltransferase 1 (CARM1) plays an important role in cell proliferation and gene expression, and is highly expressed in a variety of tumor tissues. Guided by our previous reported structure of DCPR049_12, we focused on designing and evaluating selective CARM1 inhibitors, resulting in the identification of compound 11f as a promising lead candidate. Compound 11f displayed potent inhibition of CARM1 (IC50 = 9 nM). Comprehensive evaluations, including in vitro metabolic stability assessments, molecular modelling, cellular studies, and in vivo anti-tumor studies, confirmed that it induced cancer cell apoptosis and specifically inhibited CARM1's methylation function. Notably, compound 11f displayed significant anti-proliferative effects on colorectal cancer cell lines, showcasing its potential for targeted therapies against CARM1-related diseases. This study provides valuable insights for the future development of specific and effective CARM1 inhibitors.


Asunto(s)
Neoplasias Colorrectales , Proteína-Arginina N-Metiltransferasas , Humanos , Línea Celular , Apoptosis , Neoplasias Colorrectales/tratamiento farmacológico
18.
J Psychiatr Res ; 172: 108-118, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38373372

RESUMEN

In the neurodevelopmental model of schizophrenia, minor physical anomalies (MPAs) are considered neurodevelopmental markers of schizophrenia. To date, there has been no research to evaluate the interaction between MPAs. Our study built and used a machine learning model to predict the risk of schizophrenia based on measurements of MPA items and to investigate the potential primary and interaction effects of MPAs. The study included 470 patients with schizophrenia and 354 healthy controls. The models used are classical statistical model, Logistic Regression (LR), and machine leaning models, Decision Tree (DT) and Random Forest (RF). We also plotted two-dimensional scatter diagrams and three-dimensional linear/quadratic discriminant analysis (LDA/QDA) graphs for comparison with the DT dendritic structure. We found that RF had the highest predictive power for schizophrenia (Full-training AUC = 0.97 and 5-fold cross-validation AUC = 0.75). We identified several primary MPAs, such as the mouth region, high palate, furrowed tongue, skull height and mouth width. Quantitative MPA analysis indicated that the higher skull height and the narrower mouth width, the higher the risk of schizophrenia. In the interaction, we further identified that skull height and mouth width, furrowed tongue and skull height, high palate and skull height, and high palate and furrowed tongue, showed significant two-item interactions with schizophrenia. A weak three-item interaction was found between high palate, skull height, and mouth width. In conclusion, we found that the two machine learning methods showed good predictive ability in assessing the risk of schizophrenia using the primary and interaction effects of MPAs.


Asunto(s)
Esquizofrenia , Lengua Fisurada , Humanos , Modelos Logísticos , Aprendizaje Automático , Modelos Estadísticos
19.
Angew Chem Int Ed Engl ; 63(16): e202401120, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38326521

RESUMEN

Multi-resonance thermally activated delayed fluorescence (MR-TADF) materials hold great promise for advanced high-resolution organic light-emitting diode (OLED) displays. However, persistent challenges, such as severe aggregation-caused quenching (ACQ) and slow spin-flip, hinder their optimal performance. We propose a synergetic steric-hindrance and excited-state modulation strategy for MR-TADF emitters, which is demonstrated by two blue MR-TADF emitters, IDAD-BNCz and TIDAD-BNCz, bearing sterically demanding 8,8-diphenyl-8H-indolo[3,2,1-de]acridine (IDAD) and 3,6-di-tert-butyl-8,8-diphenyl-8H-indolo[3,2,1-de]acridine (TIDAD), respectively. These rigid and bulky IDAD/TIDAD moieties, with appropriate electron-donating capabilities, not only effectively mitigate ACQ, ensuring efficient luminescence across a broad range of dopant concentrations, but also induce high-lying charge-transfer excited states that facilitate triplet-to-singlet spin-flip without causing undesired emission redshift or spectral broadening. Consequently, implementation of a high doping level of IDAD-BNCz resulted in highly efficient narrowband electroluminescence, featuring a remarkable full-width at half-maximum of 34 nm and record-setting external quantum efficiencies of 34.3 % and 31.8 % at maximum and 100 cd m-2, respectively. The combined steric and electronic effects arising from the steric-hindered donor introduction offer a compelling molecular design strategy to overcome critical challenges in MR-TADF emitters.

20.
Psychophysiology ; 61(7): e14552, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38406999

RESUMEN

Prosocial behaviors are central to individual and societal well-being. Although the relationship between effort and prosocial behavior is increasingly studied, the impact of effort-based self-interested motivation on prosocial behavior has received less attention. In the current study, we carried out two experiments to examine the effect of motivation to obtain a reward for oneself on donation behavior and brain response. We observed that individuals who accumulated more money in the effort-expenditure rewards task (EEfRT) donated a lower proportion of their earnings. The sigmoid model fitted participants' choices in the EEfRT task, and the effort-reward bias and sigma parameters negatively correlated with the amount of money donated in the donation task. Additionally, the effort-reward bias and sigma parameters negatively predicted N2 amplitude during processing of charitable donation-related information. We propose that individuals who exhibit a lower level of effort-based self-interest motivation may allocate more cognitive control or attentional resources when processing information related to charitable donations. Our work adds weight to understanding the relationship between effort-based self-interest motivation and prosocial behavior and provides electrophysiological evidence.


Asunto(s)
Altruismo , Electroencefalografía , Potenciales Evocados , Motivación , Recompensa , Humanos , Motivación/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Potenciales Evocados/fisiología
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